The purpose is to investigate tocilizumab administration in patients with moderately to severely or sight-threatening GO (Graves' ophthalmopathy) without response to treatment with corticoid intravenous pulses. Currently, these patients only have surgery as therapeutic alternative.

The principal aim of this study is to evaluate efficacy and safety of tocilizumab treatment in order to provide a better alternative to surgery for this patients.

Further study details as provided by Hospital Clinico Universitario de Santiago:

Primary Outcome Measures:

Drug efficacy will be established as a decrease in CAS (clinical activity score) by 2 or more points in a scale of 10. [ Time Frame: It will be measured before treatment (week -4 / 0), after treatment (week 16) and after the end of the follow-up (week 40). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical response of patients who respond to treatment with tocilizumab [ Time Frame: It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40). ] [ Designated as safety issue: No ]

Evaluate the patients quality of life associated with tocilizumab treatment, using SF-36 [ Time Frame: It will be analyzed before treatment (week -4 / 0), after treatment (week 16) and once to follow up (week 40). ] [ Designated as safety issue: No ]

Determine time to recurrence during follow-up period [ Time Frame: It is measured on a weeks-time scale assessed by the physician during patient follow-up visits. ] [ Designated as safety issue: No ]

Single intravenous infusion of tocilizumab (8 mg/kg); every 4 weeks during 16 weeks.

Placebo Comparator: Sterile 0.9% Sodium Chloride

Drug: Sterile 0.9% Sodium Chloride

Single intravenous dip infusion of a sterile 0.9% sodium chloride, every four weeks during 16 weeks.

Detailed Description:

Thyroid orbitopathy or Graves´orbitopathy (GO) is manifested for inflammation of the orbital and periorbital soft tissues. Ten percent of patients with GO will have long-term serious eye problems.

The cause of the GO is complex. Autoreactive T cells recognize an autoantigen, the TSH receptor present in the orbit and thyroid follicular cell, secrete cytokines (IL-6), which stimulate the fibroblasts to synthesize glycosaminoglycan, which draws liquid produce periorbital edema and muscle, causing exophthalmos.

This approach suggests that inhibition of IL-6 can be an effective treatment for this problem on the basis that tocilizumab specifically binds to the receptors of the IL-6, both soluble and membrane-bound. Tocilizumab has been shown to inhibit signaling mediated for IL-6Rm IL-6Rs.

Eligibility

Ages Eligible for Study:

18 Years to 75 Years (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Principal Inclusion Criteria:

Patients diagnosed GO with CAS ≥ 4 and an index of severity, according EUGOGO guidelines, 1. moderately to severely or 2. sight-threatening GO, after receiving corticosteroid pulse treatment due to:

Poor response to intravenous corticosteroid pulses Or

Recurrence of the GO, after treatment with intravenous corticosteroids

Exclusion Criteria:

Orbital decompression surgery needed immediately

Active smoker

Patients who could need treatment with radioactive iodine or thyroidectomy during the study

Pregnant patient or patient who is planning to become pregnant during the study

History of chronic recurrent or active infection

History of intestinal ulceration or diverticulitis

Patients with a history of chronic liver disease or liver disorders: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) above 5 times upper limit of normal (ULN)

History of HIV, hepatitis C or hepatitis B Positive

Neutrophil count < 0.5 × 109/L or a platelet count < 50×103/μL

Simultaneous use or contraindications to the use of immunosuppressive agents

A treatment with another investigational drug within four weeks of selection or five half-lives of study drug

Cardiovascular or cerebrovascular disease clinically significant

Uncontrolled diabetes mellitus

Use of corticosteroids during four weeks before to inclusion period

History of reactions or anaphylactic allergic severe human monoclonal antibodies, humanized or murine

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01297699